Abstract
Rationale
Recent studies have suggested that the medial prefrontal cortex (mPFC) plays an important role in the development of sensitization to cocaine. In particular, a recent report proposed that sensitization is associated with a decreased dopamine D2 receptor function in the mPFC. The present study was designed to further examine the involvement of mPFC dopamine D2 receptors in cocaine sensitization.
Objectives
The experiments described below sought to determine the effects of acute or repeated intra-mPFC injections of the dopamine D2 antagonist sulpiride on subsequent motor-stimulant and nucleus accumbens dopamine responses to cocaine.
Methods
Rats received bilateral cannulae implants above the ventral mPFC for microinjections and above the nucleus accumbens for in vivo microdialysis. Initial studies examined the effects of intra-mPFC sulpiride pretreatment on the acute motor-stimulant and nucleus accumbens dopamine responses to cocaine. Follow-up studies determined the effects of repeated intra-mPFC sulpiride injections on subsequent behavioral and nucleus accumbens dopamine responses to a cocaine challenge.
Results
Intra-mPFC sulpiride enhanced the cocaine-induced increases in motor activity and dopamine overflow in the nucleus accumbens. Repeated intra-mPFC sulpiride induced behavioral and neurochemical cross-sensitization to cocaine.
Conclusions
The data support previous findings that sensitization is associated with a decrease in dopamine D2 receptor function in the mPFC.
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Acknowledgements
All research efforts were financially supported by grants DA13470 and DA15965 (J.D.S.) from the National Institute on Drug Abuse.
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Steketee, J.D., Walsh, T.J. Repeated injections of sulpiride into the medial prefrontal cortex induces sensitization to cocaine in rats. Psychopharmacology 179, 753–760 (2005). https://doi.org/10.1007/s00213-004-2102-5
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DOI: https://doi.org/10.1007/s00213-004-2102-5